Bacterial production of β-lactamases represents the most clinically concerning mechanism of resistance to β-lactam antibiotics in Gram negative bacteria. The emergence of many recent β-lactamase variants (>1600 new enzymes) jeopardizes the efficacy of both the latest developed antibiotics and the combination of β-lactam/β-lactam inhibitor (BLI) (e.g., the formulation ampicillin and clavulanic acid are ineffective against bacteria expressing inhibitor resistant TEM and SHV β-lactamases). At the moment, boronic acids transition state inhibitors (BATSIs) represent a class of BLIs in development, as shown by the advancement of a combination of a boronic acid inhibitor (RPX7009 currently developed by the Medicines Company) with meropenem (a carbapenem), in clinical trials (Clinical Trials Phase 1 registration number NCT01897779, RPX7009 is joined with RPX2014). Carbavance (meropenem/RPX7009) is particularly targeted against KPC (Klebsiella pneumoniae carbapenemase)-producing carbapenem-resistant Enterobacteriaceae (CRE).
α-Amidomethaneboronic acid is a recurring core-structure in biologically active and important boron-containing compounds. α-Amidomethaneboronate unit is the basic structure of peptidoboronic acids, a class of peptidomimetics largely explored to target different clinically relevant proteases. For example, the anticancer Velcade is a dipeptidyl boronic acid (Phe-boroLeu) acting as proteasome inhibitor, while derivatives of the type Val-boroPro or Pro-boroAla have been investigated as dipeptidyl peptidase-4 inhibitors for the treatment of diabetes. The same skeleton is part also of simpler acylamidomethaneboronic acids, reported as subtilisin and α-chymotrypsin inhibitors and used as fluorescent carbohydrate sensors.